Pasquale Mordasini

Stent Placement in Acute Cerebral Artery Occlusion Use of a Self-Expandable Intracranial Stent for Acute Stroke Treatment

Background and Purpose— Stent placement has been applied in small case series as a rescue therapy in combination with different thrombolytic agents, percutaneous balloon angioplasty (PTA), and mechanical thromboembolectomy (MT) in acute stroke treatment. These studies report a considerable mortality and a high rate of intracranial hemorrhages when balloon-mounted stents were used. This study was performed to evaluate feasibility, efficacy, and safety of intracranial artery recanalization for acute ischemic stroke using a self-expandable stent. Methods— All patients treated with an intracranial stent for acute cerebral artery occlusion were included. Treatment comprised intraarterial thrombolysis, thromboaspiration, MT, PTA, and stent placement. Recanalization result was assessed by follow-up angiography immediately after stent placement. Complications related to the procedure and outcome at 3 months were assessed. Results— Twelve patients (median NIHSS 14, mean age 63 years) were treated with intracranial stents for acute ischemic stroke. Occlusions were located in the posterior vertebrobasilar circulation (n=6) and in the anterior circulation (n=6). Stent placement was feasible in all procedures and resulted in partial or complete recanalization (TIMI 2/3) in 92%. No vessel perforations, subarachnoid, or symptomatic intracerebral hemorrhages occurred. One dissection was found after thromboaspiration and PTA. Three patients (25%) had a good outcome (mRS 0 to 2), 3 (25%) a moderate outcome (mRS 3), and 6 (50%) a poor outcome (mRS 4 to 6). Mortality was 33.3%. Conclusions— Intracranial placement of a self-expandable stent for acute ischemic stroke is feasible and seems to be safe to achieve sufficient recanalization.

National Institutes of Health Stroke Scale Score and Vessel Occlusion in 2152 Patients With Acute Ischemic Stroke

Background and Purpose— There is some controversy on the association of the National Institutes of Health Stroke Scale (NIHSS) score to predict arterial occlusion on MR arteriography and CT arteriography in acute stroke. Methods— We analyzed NIHSS scores and arteriographic findings in 2152 patients (35.4% women, mean age 66±14 years) with acute anterior or posterior circulation strokes. Results— The study included 1603 patients examined with MR arteriography and 549 with CT arteriography. Of those, 1043 patients (48.5%; median NIHSS score 5, median time to clinical assessment 179 minutes) showed an occlusion, 887 in the anterior (median NIHSS score 7/0–31), and 156 in the posterior circulation (median NIHSS score 3/0–32). Eight hundred sixty visualized occlusions (82.5%) were located centrally (ie, in the basilar, intracranial vertebral, internal carotid artery, or M1/M2 segment of the middle cerebral artery). NIHSS scores turned out to be predictive for any vessel occlusions in the anterior circulation. Best cut-off values within 3 hours after symptom onset were NIHSS scores ≥9 (positive predictive value 86.4%) and NIHSS scores ≥7 within >3 to 6 hours (positive predictive value 84.4%). Patients with central occlusions presenting within 3 hours had NIHSS scores <4 in only 5%. In the posterior circulation and in patients presenting after 6 hours, the predictive value of the NIHSS score for vessel occlusion was poor. Conclusions— There is a significant association of NIHSS scores and vessel occlusions in patients with anterior circulation strokes. This association is best within the first hours after symptom onset. Thereafter and in the posterior circulation the association is poor.

Factors that determine penumbral tissue loss in acute ischaemic stroke

The goal of acute stroke treatment with intravenous thrombolysis or endovascular recanalization techniques is to rescue the penumbral tissue. Therefore, knowing the factors that influence the loss of penumbral tissue is of major interest. In this study we aimed to identify factors that determine the evolution of the penumbra in patients with proximal (M1 or M2) middle cerebral artery occlusion. Among these factors collaterals as seen on angiography were of special interest. Forty-four patients were included in this analysis. They had all received endovascular therapy and at least minimal reperfusion was achieved. Their penumbra was assessed with perfusion- and diffusion-weighted imaging. Perfusion-weighted imaging volumes were defined by circular singular value decomposition deconvolution maps (Tmax > 6 s) and results were compared with volumes obtained with non-deconvolved maps (time to peak > 4 s). Loss of penumbral volume was defined as difference of post- minus pretreatment diffusion-weighted imaging volumes and calculated in per cent of pretreatment penumbral volume. Correlations between baseline characteristics, reperfusion, collaterals, time to reperfusion and penumbral volume loss were assessed using analysis of covariance. Collaterals (P = 0.021), reperfusion (P = 0.003) and their interaction (P = 0.031) independently influenced penumbral tissue loss, but not time from magnetic resonance (P = 0.254) or from symptom onset (P = 0.360) to reperfusion. Good collaterals markedly slowed down and reduced the penumbra loss: in patients with thrombolysis in cerebral infarction 2 b-3 reperfusion and without any haemorrhage, 27% of the penumbra was lost with 8.9 ml/h with grade 0 collaterals, whereas 11% with 3.4 ml/h were lost with grade 1 collaterals. With grade 2 collaterals the penumbral volume change was -2% with -1.5 ml/h, indicating an overall diffusion-weighted imaging lesion reversal. We conclude that collaterals and reperfusion are the main factors determining loss of penumbral tissue in patients with middle cerebral artery occlusions. Collaterals markedly reduce and slow down penumbra loss. In patients with good collaterals, time to successful reperfusion accounts only for a minor fraction of penumbra loss. These results support the hypothesis that good collaterals extend the time window for acute stroke treatment.

Three-Month and Long-Term Outcomes and Their Predictors in Acute Basilar Artery Occlusion Treated With Intra-Arterial Thrombolysis

Background and Purpose— Intra-arterial thrombolysis can be used for treatment of basilar artery occlusion. Predictors of outcome before initiation of treatment are of special interest. Methods— From 1992 to 2010, we treated 106 consecutive patients with basilar artery occlusion with intra-arterial thrombolysis. Baseline characteristics, treatment, clinical course, and 3-month and long-term outcomes (≥12 months) were assessed. Outcome parameters were vessel recanalization after treatment, complications, modified Rankin scale (mRS) score, and mortality after 3 months and in the long-term. Results— At 3 months, clinical outcome was good (mRS score, 0–2) in 33.0% of the patients and moderate (mRS score, 3) in 11.3%. Mortality was 40.6%. Partial or complete recanalization was achieved in 69.8% of the patients, and symptomatic intracranial hemorrhage occurred in 1 patient (0.9%). Between 3-month and long-term follow-up, 22 survivors (40.8%) showed clinical improvement of at least 1 point on the mRS score, 29 (53.7%) were functionally unchanged, and 3 (5.7%) showed functional worsening (P<0.0001). Multivariate analysis identified diabetes as a predictor of poor vessel recanalization (P=0.028). Low baseline National Institutes of Health Stroke Scale score was identified as a predictor of good or moderate clinical outcome (P<0.0001) and survival (P=0.001) at 3 months, and younger age was identified as an additional predictor of survival (P=0.012). For prediction of long-term clinical outcome, age was also an independent predictor (P=0.018). Conclusions— In our series, intra-arterial thrombolysis as treatment of basilar artery occlusion was safe. National Institutes of Health Stroke Scale score at admission and age were identified as predictors of outcome, and these predictors should be considered for treatment allocation in future randomized trials.

Technical Feasibility and Application of Mechanical Thrombectomy with the Solitaire FR Revascularization Device in Acute Basilar Artery Occlusion

BACKGROUND AND PURPOSE: Acute BAO is a devastating neurological condition associated with a poor clinical outcome and a high mortality rate. Recanalization has been identified as a major prognostic factor for good outcome in BAO. Mechanical thrombectomy using retrievable stents is an emerging treatment option for acute stroke. First clinical trials using stent retrievers have shown promising high recanalization rates. However, these studies mainly included large artery occlusions in the anterior circulation with only a few or single cases of BAO. Therefore, the purpose of this study was to evaluate technical feasibility, safety, and efficacy of mechanical thrombectomy using retrievable stent in the treatment of acute BAO. MATERIALS AND METHODS: Fourteen consecutive patients with BAO undergoing endovascular therapy using retrievable stents (Solitaire FR Revascularization Device) were included. Additional multimodal treatment approaches included thromboaspiration, intravenous and/or intra-arterial thrombolysis, and PTA/ permanent stent placement. Recanalization rates after multimodal therapy and stent retrieval were determined. Clinical outcome and mortality were assessed 3 months after treatment. RESULTS: Median patient age was 64.5 years (range 55–85). Median NIHSS score at presentation was 21 (range 5–36). Overall, successful recanalization (TICI 3 or 2b) was achieved in all patients (TICI 3 in 78.6%, 11/14). In 4 patients (28.6%), insufficient recanalization after stent retrieval was due to an underlying atherosclerotic stenosis. Additional deployment of a permanent intracranial stent was performed in 3 patients (21.4%) and PTA alone in 1 patient (7.1%), resulting in final TICI 3 in 1 patient and TICI 2b in 3 patients. Stent retrieval alone was performed in 4 patients (28.6%). Average number of device passes was 1.3 (range 1–3). Median procedure time to maximal recanalization was 47 minutes (range 10–252). No device-related complications or thromboembolic occlusion of a previously unaffected artery occurred. There was no symptomatic intracranial hemorrhage. At 3 months, good functional outcome (mRS 0–2) was observed in 28.6% (4/14); overall mortality was 35.7% (5/14). CONCLUSIONS: A multimodal endovascular approach using retrievable stents in BAO has high recanalization rates, with very low complication rates. Underlying atherothrombotic stenotic lesions of the basilar artery may still necessitate additional permanent stent placement to achieve complete recanalization.

Impact of Retrievable Stents on Acute Ischemic Stroke Treatment

BACKGROUND AND PURPOSE: Retrievable stents combine the high recanalization rate of stents and the capability of removing the thrombus offered by mechanical thrombectomy devices. We hypothesized that retrievable stents shorten time to recanalization in the multimodal approach for endovascular stroke treatment. MATERIALS AND METHODS: Forty consecutive patients with acute ischemic stroke and undergoing endovascular therapy were included. Treatment included thromboaspiration, thrombus disruption, thrombolysis, PTA, and stent placement. In 17 patients, a retrievable stent was used (group A) in addition to multimodal therapy. The remaining 23 patients constituted group B. Baseline characteristics, occlusion sites, urokinase dose, recanalization rate, and time to recanalization were compared between the groups. RESULTS: Median NIHSS scores were higher in group A compared with group B on admission (19 versus 12.5; P = .018) but were not significantly different at day 1 (14 versus 10; P = .6). Intra-arterial thrombolysis was used in significantly fewer patients of group A than group B (53% versus 87%, respectively; P = .017), and median urokinase dose was lower in group A than in group B (250,000 IU versus 700,000 IU; P = .006). Time to recanalization was significantly shorter in group A compared with group B (median time to recanalization 52.5 minutes versus 90 minutes, respectively; P = .001). Recanalization rate was higher in group A than group B (94% versus 78%; P = .17). CONCLUSIONS: Addition of retrievable stents to the multimodal endovascular approach for acute ischemic stroke treatment significantly reduces time to recanalization and further increases the recanalization rate.

Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study

Background: Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation. Methods: SPION-containing patches were implanted in rats. Three animal groups were studied histologically over six months. Degradation assessment of the SPION-albumin patch was performed in vivo using MRI for iron content localization and biodistribution. Results: No SPION degradation or accumulation into the reticuloendothelial system was detected by MRI, MRI relaxometry, or histology, outside the area of the implantation patch. Concentrations from 0.01 μg/mL to 25 μg/mL were found to be hyperintense in T1-like gradient echo sequences. The best differentiation of concentrations was found in T2 relaxometry, susceptibility-sensitive gradient echo sequences, and in high repetition time T2 images. Qualitative and semiquantitative visualization of small concentrations and accumulation of SPIONs by MRI are feasible. In histological liver samples, Kupffer cells were significantly correlated with postimplantation time, but no differences were observed between sham-treated and induction/no induction groups. Transmission electron microscopy showed local uptake of SPIONs in macrophages and cells of the reticuloendothelial system. Apoptosis staining using caspase showed no increased toxicity compared with sham-treated tissue. Implanted SPION patches were relatively inert with slow, progressive local degradation over the six-month period. No distant structural alterations in the studied tissue could be observed. Conclusion: Systemic bioavailability may play a role in specific SPION implant toxicity and therefore the local degradation process is a further aspect to be assessed in future studies.

Endovascular therapy in 201 patients with acute symptomatic occlusion of the internal carotid artery

Endovascular therapy is used increasingly for treatment of acute symptomatic internal carotid artery (ICA) occlusion, although randomized trials are lacking. Predictors of outcome are therefore of special interest.

In vivo evaluation of the first dedicated combined flow-restoration and mechanical thrombectomy device in a swine model of acute vessel occlusion.

BACKGROUND AND PURPOSE: The use of self-expanding retrievable stents is an emerging and promising treatment strategy for acute stroke treatment. The concept combines the advantages of stent deployment with immediate flow-restoration and of mechanical thrombectomy with definitive thrombus removal. The present study was performed to gain more knowledge about the principle of combined flow restoration and thrombectomy in an established animal model using radiopaque thrombi evaluating efficiency, thrombus-device interaction and possible complications of the first dedicated flow-restoration and mechanical thrombectomy device. MATERIALS AND METHODS: The Solitaire FR (4 × 20 mm) was evaluated in 15 vessel occlusions in an established animal model in swine. Flow-restoration effect at T0, T5, and T10; recanalization rate after retrieval; thromboembolic events; and complications were assessed. Radiopaque thrombi (10-mm length) were used for visualization of thrombus-device interaction during application and retrieval. RESULTS: Immediate flow restoration was achieved in 80% of occlusions. Mean percentage of recanalization compared with the initial vessel diameter at T0 was 30.8%; at T5, 30.7%; and at T10, 25.4%. Re-occlusion occurred in 20.0% between T0 and T5 and in 13.3% between T5 and T10. Complete recanalization (TICI 3) after retrieval was achieved in 86.7%. In 2 cases (13.3%), partial recanalization was achieved, with the remaining thrombus in a side branch (TICI 2b). No thromboembolic event was observed. The assessment of thrombus-device interaction illustrated the compression of the thrombus against the vessel wall during deployment leading to partial flow restoration. During retrieval, the thrombus was retained by the stent struts even during the passage of vessel curvatures. CONCLUSIONS: The Solitaire FR is a safe and effective combined flow-restoration and thrombectomy device in vivo. Partial flow restoration is achieved by thrombus compression immediately after deployment, but flow restoration decreases afterward until final retrieval results in maximal recanalization.

Direct Mechanical Intervention Versus Combined Intravenous and Mechanical Intervention in Large Artery Anterior Circulation Stroke A Matched-Pairs Analysis

Background and Purpose— Five randomized controlled trials have consistently shown that mechanical thrombectomy (MT) in addition to best medical treatment (±intravenous tissue-type plasminogen activator) improves outcome after acute ischemic stroke in patients with large artery anterior circulation stroke. Whether direct MT is equally effective as combined intravenous thrombolysis with MT (ie, bridging thrombolysis) remains unclear. Methods— We retrospectively compared clinical and radiological outcomes in 167 bridging patients with 255 patients receiving direct MT because of large artery anterior circulation stroke. We matched all patients from the direct MT group who would have qualified for intravenous tissue-type plasminogen activator with controls from the bridging group, using multivariate and propensity score analyses. Functional independence was defined as modified Rankin Scale score of 0 to 2. Results— From February 2009 to August 2014, 40 patients from the direct MT group would have qualified for bridging thrombolysis but were treated with MT only. Clinical and radiological characteristics did not differ from the bridging cohort, except for higher rates of hypercholesterolemia (P=0.019), coronary heart disease (P=0.039), and shorter intervals from symptom onset to endovascular intervention (P=0.01) in the direct MT group. Functional independence, mortality, and intracerebral hemorrhage rates did not differ (P>0.1). After multivariate matching analysis outcome in both groups did not differ, except for lower rates of asymptomatic intracerebral hemorrhage (P=0.023) and lower mortality (P=0.007) in the direct MT group. Conclusions— In patients with large anterior circulation stroke, direct mechanical intervention seems to be equally effective as bridging thrombolysis. A randomized trial comparing direct MT with bridging therapy is warranted.